Cell-free microRNA expression profiles in malignant effusion associated with patient survival in non-small cell lung cancer

PLoS One. 2012;7(8):e43268. doi: 10.1371/journal.pone.0043268. Epub 2012 Aug 24.

Abstract

Objective: MicroRNAs (miRNAs) expression is altered in cancer cells, and miRNAs could serve as diagnostic and prognostic biomarker for cancer patients. This study was designed to analyze circulating miRNAs expression in the malignant pleural effusion (MPE) and their association with patient survival in non-small cell lung cancer (NSCLC).

Methods: Pleural effusion from 184 patients with NSCLC and MPE were collected. MiRNA microarray and bioinformatics interpretation were used to evaluate miRNA expression profiles in 10 NSCLC patients with different survival prognosis. Associations were validated in 184 patients (randomly classified into training and validation set with equal number in each group) using quantitative RT-PCR. Risk scores were formulated based on the expression signature of miRNAs. Clinical data, such as patient survival, were collected for correlation analysis.

Results: Thirty-three miRNAs were found to be altered more than two-fold by microarray in malignant effusions between longer-survival and shorter-survival groups, and levels of five miRNAs (miRNA-93, miRNA-100, miRNA-134, miRNA-151 and miRNA-345) were significantly associated with overall survival. High expression of miR-100 and low expression of miRNA-93, miRNA-134, miRNA-151 and miRNA-345 were associated with poor survival in both the training and validation cohort. Patients with high risk scores had overall poor survival compared to the patients with low risk scores. Risk score was an independent predictor of patient survival.

Conclusions: Expression patterns of miRNAs are systematically altered in MPE of patient with NSCLC. The five miRNA signature from the effusion may serve as a predictor for the overall survival of patients with lung cancers.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carcinoma, Non-Small-Cell Lung / genetics*
  • Computational Biology
  • Female
  • Gene Expression Regulation, Neoplastic / genetics
  • Humans
  • Kaplan-Meier Estimate
  • Lung Neoplasms / genetics*
  • Male
  • MicroRNAs / genetics*
  • Middle Aged
  • Pleural Effusion, Malignant / genetics*
  • Proportional Hazards Models

Substances

  • MicroRNAs

Grants and funding

This work was supported by the National Natural Science Foundation of China (81101552), the Natural Science Foundation of Jiangsu Province (BK2011571), Specialized Research Fund for the Doctoral Program of Higher Education (20100091120002), and the Fundamental Research Funds for the Central Universities (1118021418 and 1118021406). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.